Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression

• Published in: Frontiers in immunology Vol. 11; p. 588322
• Main Authors: Masson Regnault, Marie, Frouin, Eric, Jéru, Isabelle, Delwail, Adriana, Charreau, Sandrine, Barbarot, Sébastien, Néel, Antoine, Masseau, Agathe, Puéchal, Xavier, Kyndt, Xavier, Gayet, Stephane, Lifermann, François, Asli, Bouchra, Balguerie, Xavier, Blanchard-Delaunay, Claire, Aubin, François, Rizzi, Rita, Rongioletti, Franco, Boyé, Thierry, Gusdorf, Laurence, Bessis, Didier, Morel, Franck, Hainaut, Ewa, Lipsker, Dan, Lecron, Jean-Claude
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 26.11.2020; Frontiers Media S.A
• Subjects: cytokines; IL-1; IL-1 antagonist; Immunology; inflammasome; Life Sciences; PBMC (peripheral blood mononuclear cells); Schnitzler syndrome; IL-1; PBMC (peripheral blood mononuclear cells); inflammasome; cytokines; Schnitzler syndrome; IL-1 antagonist; ex vivo
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.588322

Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. To determine v cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS ( = 0.04). Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra.